Genetics最新文献_第5页

Effectiveness of CRISPR-Cas in Sensitizing Bacterial Populations with Plasmid-Encoded Antimicrobial Resistance. CRISPR-Cas在致敏质粒编码抗菌素耐药性细菌群体中的有效性

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-23 DOI: 10.1093/genetics/iyaf192

Johannes Kippnich, Fabienne Benz, Hildegard Uecker, Franz Baumdicker

{"title":"Effectiveness of CRISPR-Cas in Sensitizing Bacterial Populations with Plasmid-Encoded Antimicrobial Resistance.","authors":"Johannes Kippnich, Fabienne Benz, Hildegard Uecker, Franz Baumdicker","doi":"10.1093/genetics/iyaf192","DOIUrl":"https://doi.org/10.1093/genetics/iyaf192","url":null,"abstract":"The spread of bacteria resistant to antibiotics poses a serious threat to human health. Genes that encode antibiotic resistance are often harbored on plasmids, extra-chromosomal DNA molecules found in bacteria. The emergence of multiresistance plasmids is particularly problematic and demands the development of new antibiotics and alternative strategies. CRISPR-Cas derived tools with their sequence specificity offer a promising new approach to combating antibiotic resistance. By introducing CRISPR-Cas encoding plasmids that %specifically target antibiotic resistance genes on plasmids, the susceptibility of bacteria to conventional antibiotics can be restored. However, genetic variation within bacterial populations can hinder the effectiveness of such CRISPR-Cas tools by allowing some mutant plasmids to evade CRISPR-mediated cleaving or gene silencing. In this study, we develop a model to test the effectiveness of CRISPR-Cas in sensitizing bacterial populations carrying resistance on non-transmissible plasmids and assess the success probability of a subsequent treatment with conventional antibiotics. We evaluate this probability according to the target interference mechanism, the copy number of the resistance-encoding plasmid, and its compatibility with the CRISPR-Cas encoding plasmid. Our results identify promising approaches to revert antibiotic resistance with CRISPR-Cas encoding plasmids: A DNA-cleaving CRISPR-Cas system on a plasmid incompatible with the targeted plasmid is most effective for low copy numbers, while for resistance plasmids with higher copy numbers gene silencing by CRISPR-Cas systems encoded on compatible plasmids is the superior solution.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

gyōza: a Snakemake workflow for modular analysis of deep-mutational scanning data. gyōza：一个用于深度突变扫描数据的模块化分析的Snakemake工作流。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-22 DOI: 10.1093/genetics/iyaf199

Romain Durand, Alicia Pageau, Christian R Landry

引用次数: 0

Identification and characterization of components of the Candida albicans inner kinetochore. 白色念珠菌内着丝点成分的鉴定与表征。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-19 DOI: 10.1093/genetics/iyaf201

Emily H Xiong, Ci Fu, Zhen-Yuan Lin, Cassandra J Wong, Kayla Nathwani, Hansen Wang, Anne-Claude Gingras, Nicole Robbins, Leah E Cowen

{"title":"Identification and characterization of components of the Candida albicans inner kinetochore.","authors":"Emily H Xiong, Ci Fu, Zhen-Yuan Lin, Cassandra J Wong, Kayla Nathwani, Hansen Wang, Anne-Claude Gingras, Nicole Robbins, Leah E Cowen","doi":"10.1093/genetics/iyaf201","DOIUrl":"https://doi.org/10.1093/genetics/iyaf201","url":null,"abstract":"Despite the significant global health burden posed by Candida albicans, a large proportion of its genome has yet to be characterized. While insights from model yeasts have historically provided valuable functional clues, their utility is approaching its limits given the increasing evidence of divergence across fungal species. The C. albicans inner kinetochore is a poorly characterized cellular structure. In particular, the constitutive centromere-associated network (CCAN) has only four previously known components, likely due to DNA sequence divergence between orthologous complex members from Saccharomyces cerevisiae or Schizosaccharomyces pombe. Here, we leveraged a structure-focused approach to identify seven components of the C. albicans CCAN. Phenotypic characterization of loss-of-function mutants confirmed important roles in fitness and cell cycle progression for various kinetochore subunits. Furthermore, protein interactions identified through affinity purification-mass spectrometry as well as confocal microscopy confirmed the interaction and localization of these predicted kinetochore components with known kinetochore members. Overall, this work significantly enhances our understanding of a key cellular structure in C. albicans and underscores the urgent need for pathogen-specific research to better understand its unique biological mechanisms.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of toxin/antidote genes in the maintenance and evolution of accessory chromosomes in Fusarium. 毒素/解毒剂基因在镰刀菌副染色体维持和进化中的作用。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-19 DOI: 10.1093/genetics/iyaf197

Linnea Sandell, Adrian Forsythe, Anna Mirandola, Samuel Jorayev, Andrew S Urquhart, Alexandra Granger Farbos, Sven J Saupe, Aaron A Vogan

{"title":"The role of toxin/antidote genes in the maintenance and evolution of accessory chromosomes in Fusarium.","authors":"Linnea Sandell, Adrian Forsythe, Anna Mirandola, Samuel Jorayev, Andrew S Urquhart, Alexandra Granger Farbos, Sven J Saupe, Aaron A Vogan","doi":"10.1093/genetics/iyaf197","DOIUrl":"https://doi.org/10.1093/genetics/iyaf197","url":null,"abstract":"The genomic diversity of many fungal species is augmented by accessory chromosomes, which are variably present in individual strains. These genomic regions evolve rapidly, accumulating genes important in pathogenicity but also harbor a significant number of transposable elements (TEs). This duality suggests a trade-off: accessory chromosomes provide infection-related benefits while otherwise being deleterious due to their highly repetitive nature and contributions to genomic instability. Despite this, accessory chromosomes often appear to be stably maintained even when strains are grown on media, with no plant host. Previously, we had observed that genes homologous to meiotic drive toxin/antidote proteins from Podospora anserina (Spoks) are abundant on accessory chromosomes in various Fusarium species. Using a functionality screen in yeast, we demonstrate that some of these homologs have active toxin and antidote properties. We propose that these selfish genes could maintain accessory chromosomes during vegetative growth and may influence their spread via parasexual cycles. Finally, as Spok genes are found on the newly described TE superfamily Starships, we also present a model for how these TEs could play a role in forming accessory chromosomes and regions. These results illuminate a mysterious facet of fungal biology, a key step towards describing the origin, spread, and maintenance of pathogenicity in many fungal species.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to: Echoes of eugenics: confronting its effects in indigenous genomics. 更正：优生学的回声：面对其在本土基因组学中的影响。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-18 DOI: 10.1093/genetics/iyaf172

引用次数: 0

Genetic context of transgene insertion can influence neurodevelopment in zebrafish. 转基因插入的遗传背景可以影响斑马鱼的神经发育。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-17 DOI: 10.1093/genetics/iyaf195

Anna J Moyer, Jessica A Chrabasz, Alexia Barcus, Ji Cheng, Mary E S Capps, Robert L Lalonde, Christian Mosimann, Summer B Thyme

{"title":"Genetic context of transgene insertion can influence neurodevelopment in zebrafish.","authors":"Anna J Moyer, Jessica A Chrabasz, Alexia Barcus, Ji Cheng, Mary E S Capps, Robert L Lalonde, Christian Mosimann, Summer B Thyme","doi":"10.1093/genetics/iyaf195","DOIUrl":"10.1093/genetics/iyaf195","url":null,"abstract":"The Gal4/UAS system is used across model organisms to overexpress target genes in precise cell types and relies on generating transgenic Gal4 driver lines. In zebrafish, the Tg(elavl3:KalTA4) (HuC) Gal4 line drives robust expression in neurons. We observed an increased prevalence of swim bladder defects in Tg(elavl3:KalTA4) zebrafish larvae compared to wildtype siblings, which prompted us to investigate whether transgenic larvae display additional neurobehavioral phenotypes. Tg(elavl3:KalTA4) larvae showed alterations in brain activity, brain morphology, and behavior, including increased hindbrain size and reduced activity of the cerebellum. Bulk RNA-seq analysis revealed dysregulation of the transcriptome and suggested an increased ratio of neuronal progenitor cells compared to differentiated neurons. To understand whether these phenotypes derive from Gal4 toxicity or from positional effects related to transgenesis, we used economical low-pass whole genome sequencing to map the Tol2-mediated insertion site to chromosome eight. Reduced expression of the neighboring gene gadd45ga, a known cell cycle regulator, is consistent with increased proliferation and suggests a role for positional effects. Challenges with creating alternative pan-neuronal lines include the length of the elavl3 promoter (over 8 kb) and random insertion using traditional transgenesis methods. To facilitate the generation of alternative lines, we cloned five neuronal promoters (atp6v0cb, smaller elavl3, rtn1a, sncb, and stmn1b) ranging from 1.7 kb to 4.3 kb and created KalTA4 lines using Tol2 and the phiC31 integrase-based pIGLET system. Our study highlights the importance of using appropriate genetic controls and interrogating potential positional effects in new transgenic lines.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of genetic tools for the sea anemone Aiptasia, a model system for coral biology. 珊瑚生物学模型系统海葵遗传工具的开发。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-17 DOI: 10.1093/genetics/iyaf194

Christian Renicke, Natalie Swinhoe, Catherine Henderson, Emily Meier, Lorraine Ling, Geraldine L Keat, Shumpei Maruyama, Maitri Rangarajan-Paul, John R Pringle, Phillip A Cleves

{"title":"Development of genetic tools for the sea anemone Aiptasia, a model system for coral biology.","authors":"Christian Renicke, Natalie Swinhoe, Catherine Henderson, Emily Meier, Lorraine Ling, Geraldine L Keat, Shumpei Maruyama, Maitri Rangarajan-Paul, John R Pringle, Phillip A Cleves","doi":"10.1093/genetics/iyaf194","DOIUrl":"https://doi.org/10.1093/genetics/iyaf194","url":null,"abstract":"The reef-building corals can thrive in nutrient-poor waters because of the mutualistic symbiosis between the animal hosts and their photosynthetic dinoflagellate endosymbionts. This symbiosis is threatened by climate change and other anthropogenic stressors, so that a deeper mechanistic understanding of its function is not only of great basic biological interest but also crucial for developing rational approaches to coral conservation. The small sea anemone Aiptasia is an attractive model system for studies of this symbiosis but has been limited to date by a lack of effective genetic methods. Here, we describe the use of a simple electroporation protocol to introduce various genetic constructs [plasmid DNAs, mRNAs, and short-hairpin (sh) RNAs] into Aiptasia zygotes. Plasmid-based expression of reporter constructs in the resulting larvae was highly mosaic. In contrast, electroporation of mRNAs into zygotes resulted in uniform expression within the larvae, and success rates were similar when single or multiple mRNAs were introduced. The shRNAs were effective in knocking down expression of both co-electroporated mRNAs and endogenous genes. In this way, we could confirm the previously reported role of BRACHYURY in cnidarian embryonic development. In addition, we could show that knockdown of an Aiptasia homologue of the lysosomal-associated membrane protein 1 (Lamp1) interfered with larval uptake and/or retention of a symbiosis-compatible algal strain. The ability to use Aiptasia larvae for such reverse-genetic studies should greatly enhance the power of this model system and serve as a starting point for further development of genetic tools in Aiptasia and other cnidarians.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel modifiers of oncoprotein-mediated Polycomb inhibition in Drosophila melanogaster. 黑胃果蝇肿瘤蛋白介导的多梳抑制的新修饰剂。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-16 DOI: 10.1093/genetics/iyaf193

Samuel D Krabbenhoft, Tyler E Masuda, Yadwinder Kaur, Truman J Do, Siddhant U Jain, Peter W Lewis, Melissa M Harrison

{"title":"Novel modifiers of oncoprotein-mediated Polycomb inhibition in Drosophila melanogaster.","authors":"Samuel D Krabbenhoft, Tyler E Masuda, Yadwinder Kaur, Truman J Do, Siddhant U Jain, Peter W Lewis, Melissa M Harrison","doi":"10.1093/genetics/iyaf193","DOIUrl":"https://doi.org/10.1093/genetics/iyaf193","url":null,"abstract":"Polycomb Repressive Complex 2 (PRC2) maintains epigenetic repression through the catalysis of H3K27 trimethylation (H3K27me3), which restricts gene expression and preserves developmental gene-regulatory networks. The integrity of PRC2-mediated gene silencing depends critically on the ability of PRC2 to establish and propagate H3K27me3 beyond initial recruitment sites. The oncoproteins EZHIP and histone H3 K27M specifically inhibit this propagation by blocking the allosterically activated state of PRC2, leading to global disruption of H3K27me3 patterns and developmental abnormalities. To uncover chromatin-related pathways intersecting with PRC2 repression, we developed a Drosophila melanogaster model with tissue-specific expression of EZHIP and H3 K27M. A targeted RNAi screen of conserved chromatin regulators identified genetic modifiers that when knocked down either enhanced or suppressed developmental phenotypes driven by these PRC2 inhibitors. Strong suppressors, including the Trithorax-group proteins Ash1 and Trx, the PR-DUB complex member Asx, and the nucleoporin Nup153, restored normal development despite persistent depletion of global H3K27me3. Gene expression analyses revealed that suppression reflected reduced expression of genes aberrantly activated following PRC2 inhibition. Together, these findings highlight conserved chromatin-regulatory pathways that intersect with Polycomb to maintain transcriptional balance and support developmental homeostasis.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cubar: a versatile package for codon usage bias analysis in R. Cubar：一个通用的密码子使用偏差分析包。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-11 DOI: 10.1093/genetics/iyaf191

Mengyue Liu, Bu Zi, Hebin Zhang, Hong Zhang

引用次数: 0

A novel role for the E2F transcription factor and the ER stress sensor IRE1 in cytoplasmic DNA accumulation. E2F转录因子和内质网应激传感器IRE1在细胞质DNA积累中的新作用。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-11 DOI: 10.1093/genetics/iyaf190

Arghya Das, Yining Li, Yiting Fan, Nam-Sung Moon

{"title":"A novel role for the E2F transcription factor and the ER stress sensor IRE1 in cytoplasmic DNA accumulation.","authors":"Arghya Das, Yining Li, Yiting Fan, Nam-Sung Moon","doi":"10.1093/genetics/iyaf190","DOIUrl":"https://doi.org/10.1093/genetics/iyaf190","url":null,"abstract":"The E2F family of transcription factors are key regulators of the cell cycle in all metazoans. While they are primarily known for their role in cell cycle progression, E2Fs also play broader roles in cellular physiology, including the maintenance of exocrine tissue homeostasis. However, the underlying mechanisms that render exocrine cells particularly sensitive to E2F deregulation remain poorly understood. The Drosophila larval salivary gland (SG), like its mammalian counterpart, is an exocrine tissue that produces large quantities of \"glue proteins\" in the endoplasmic reticulum (ER). Here, we show that E2F activity is important for the exocrine function of the Drosophila SG. The loss of de2f1b, an alternatively spliced isoform of Drosophila E2F1, leads to elevated DNA damage and accumulation of cytoplasmic DNA (cytoDNA) in the SGs. Surprisingly, we found that IRE1, a key sensor of the unfolded protein response, is required for ER homeostasis during development that is critical for preventing cytoDNA accumulation in the SG. Importantly, we found evidence demonstrating that IRE1 activity is attenuated in de2f1b-deficient SGs, contributing to ER dysfunction and cytoDNA accumulation. Together, these findings reveal an unanticipated link between ER homeostasis and cytoDNA processing and offer mechanistic insights into why exocrine tissues are particularly vulnerable to E2F deregulation.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0